TASK 2 - BASAL GANGLIA Flashcards
basal ganglia
= large set of nuclei
- caudate, putamen, globus pallidus: motor components
- telencephalon, diencephalon (sub thalamic nuclei), mesencephalon (substantiva nigra)
- links most of the cerebral cortex with upper motor neurones in M1, premotor cortex and in the brainstem
role of basal ganglia in movement
- (+ cerebellum) influence movement by regulating activity of upper motor neurons –> no direct projection to local circuit or lower motor neurones
- facilitate movement initiation
- facilitate suppression of competing motor programs that would otherwise interfere with expression of goal-directed behaviour
- modulation of activity in anticipation of and during movements (smooth movements)
input nuclei
- cortex = largest input to basal ganglia; only primary visual + auditory cortex have no projections to the striatum
1. striatum: almost all input; from much of cerebral cortex (mostly from frontal and parietal lobes, followed by temporal, insular and cingulate cortices) - -> corticospinal pathway = multiple pathways serving different functions
a. caudate
b. putamen
2. substantia nigra pars compacta
input nuclei
1. striatum
- input zone, destinations of most pathways + incoming axons from the cerebral cortex and other parts of the brain
- medium spinal neurones = large dendritic trees that can integrate various inputs
- GABAergic neurones
- functionally subdivided to its inputs –> reflects specialisation of cortical areas that provide input
striatum
1a. caudate
- input from association cortices + motor areas in frontal lobe that control eye movements (FEF)
- occumolotor loop
- anticipatory discharge of eye movements
striatum
1b. putamen
- input from primary, secondary somatic sensory cortices in parietal lobe + secondary (extrastriate) visual cortices in occipital and temporal lobes + premotor and motor cortices in frontal lobe + auditory association areas in the temporal lobe
- motor loop
- anticipatory discharge of limb and trunk movements
- activity in these cells encode decision to move toward a goal
input nuclei
2a. substantia nigra pars compacta
- input: main dopaminergic aminergic inputs originate
- inputs relatively far from the initial segment of the medium spiny neurone axon
- neurones exhibit very little spontaneous activity and must simultaneously receive many excitatory inputs from cortical and nigral neurones to overcome stabilising influence of this potassium conductance (which remains a stable resting membrane potential, close to depolarisation)
output nuclei
- major pathways that allow basal ganglia to influence activity of upper motor neurones located in motor cortex and brainstem; 2 pathways
- GABAergic neurones/output = high levels
- activity prevents unwanted movements by tonically inhibiting cells in thalamus and superior colliculus
1. pallidum: main sources of output
a. globus pallidus: large number of myelinated axons (pale)
b. substantia nigra pars reticular: reticular/netlike form
pallidum
3. globus pallidus
- pathway to cortex
1. globus pallidus internal (GPi)
2. relays in ventral anterior + ventral lateral nuclei of dorsal thalamus
3. project directly to motor areas (M1, SMA, PFC) - motor loop: multiple areas of cortex –> processing in basal ganglia and thalamus –> terminating in motor areas
pallidum
2b. substantia nigra pars reticulata
- control head and eye movements
1. substantia nigra pars reticulata (SNr)
2. project to + terminate in superior colliculus (initiation of eye movement) - more direct: without intervening relay in thalamus
- many also project to thalamus to relay info to frontal eye fields and premotor cortex
- subthalamic nuclei
- ventral thalamus
- diencephalon
direct pathway
- activation of medium spiny neurones in input nuclei (= striatum)
- inhibition of GPi
- disinhibition of ventral thalamus
- activation of frontal cortex
direct pathway
- dopamine pathway
- substantia nigra (SNc) excites direct pathway via acting on D1 receptor –> striatum excited = inhibits GBi MORE
- ENHANCES EFFECT = more wanted movement (centre action is strongly supported)
indirect pathway
- activation of striatum
- inhibition of GPe
- disinhibition of STN
- MORE activation of GPi
- MORE inhibition of thalamus
- NO activation of frontal cortex
indirect pathway
- dopamine pathway
- substantia nigra (SNc) inhibits indirect pathway via acting on different type of D2 receptor (D2) –> striatum inhibited = inhibits GPe LESS
- REDUCES EFFECT = more unwanted movement (surrounding actions more uncontrolled)
centre-surround functional organisation
- direct pathway = centre = activation of intended motor programs
- -> facilitation of voluntary movements
- indirect pathway = surround = suppression of competing motor programs
- -> suppression of inappropriate movements
dopamine pathway
- internal pathway
- role: contribute to reward-related modulation of behaviour
- EXCITES direct pathway
- INHIBITS indirect pathway
basal ganglia disorders
- Parkinson’s disease
= hypokinetic movement disorder
= failure of disinhibition
- causes: loss of nigrostriatal dopaminergic neurones
- results in abnormally high inhibitory output of the basal ganglia –> lesser thalamic activation of upper motor neurones
- motor symptoms: resting tremor, slowness of movement (= bradykinesia); diminished facial expressions, lack associated movements (= akinesia) –> failure of normal disinhibition
- cognitive symptoms: lack of cognitive drive/motivation, decision making deficits; sometimes associated with dementia
- any movement is difficult to initiate + once initiated often difficult to terminate
- not able to act on internal cues BUT on external cues
Parkinson’s disease
- pathways
dopamine pathways degenerated:
- less facilitation of direct pathway = less activation of voluntary movements
- increases responsiveness of direct pathway to corticospinal input
- more inhibition of thalamus - less reduction = suppression of inappropriate movements
- decreases responsiveness of indirect pathway to input
- more inhibition of thalamus
- -> MORE INHIBITION = less movement initiation; cortex almost impossible to activate
Parkinson’s disease
- treatment
- l-DOPA
- stem cells, gene therapy
- deep brain stimulation: GPe, STN, GPi
basal ganglia diseases
- Huntington’s disease
= hyperkinetic movement disorder
= failure of Inhibition
- causes: degeneration of medium spiny neurons (striatum) that project to the globus pallidus (GBe) –> atrophy of caudate and putamen (striatum)
- results in abnormal activation of GPe –> reduces excitatory output of STN to GPi + inhibitory outflow of basal ganglia –> without restraining influence upper motor neurones can be activated by inappropriate signals
- symptoms: involuntary movements; alteration in mood/change in personality (increased irritability…); defects of memory and attention; rapid, jerky motions with no clear purpose (= choreiform movements)
Huntington’s disease
- pathways
medium spiny neurones degenerated = GBe degenerated:
- more inhibition of direct pathway on GPe = more activation of voluntary movements
- more activation of thalamus - less activation of indirect pathway on GPe = less suppression of involuntary movements
- more activation of thalamus
- -> MORE ACTIVATION = less control of movements; cortex easily activated
Huntington’s disease
- treatment
- deep brain stimulation
- gene therapy: antisense treatment
cortico-striatal-thalamic loops
1. motor loop
= action, movement
- motor areas (SMA)
- putamen
- lateral GPi
- ventral lateral + ventral anterior thalamic nuclei
